Auxin biosynthesis inhibitor

ABSTRACT

An object of the present invention is to provide an auxin biosynthesis inhibitor superior to L-AOPP. The object can be attained by a compound represented by general formula (I): wherein, R 1  to R 5  and X are the same as defined in the specification or a salt or solvate thereof.

TECHNICAL FIELD

The present invention relates to an auxin biosynthesis inhibitor, and aninhibitor of tryptophan aminotransferase working in the auxinbiosynthetic pathway, as well as methods for using the inhibitors.

BACKGROUND ART

Auxin is a class of plant hormones and involved in various phases suchas development, growth and environmental responses of plants. Thesubstance most ubiquitously present as a natural auxin is indole aceticacid (IAA) and natural auxins such as indolebutyric acid (IBA) and4-chloroindoleacetic acid are also known. In contrast, as syntheticauxins, p-chlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid(2,4-D), 2-methyl-4-chlorophenoxybutyric acid (MCPB) and the like areknown.

IAA, a natural auxin, is instable. In addition, a plant has adecomposition pathway thereof within the body. Therefore, a syntheticauxin is generally used for agriculture. For example,p-chlorophenoxyacetic acid is used as a fruit set accelerator fortomatoes and eggplants. Furthermore, 2,4-D is used as a herbicide and anagent for culturing a plant tissue, and MCPB is a selective herbicideused in rice paddies.

Auxins are biologically synthesized through complicated pathways. To bemore specific, the presence of two pathways through or not throughL-tryptophan has been confirmed. The pathway through L-tryptophan isfurther branched in 4 or more pathways, which are separately catalyzedby different enzymes (FIG. 1). Up to present, as substances inhibitingbiosynthesis of auxin, L-α-(2-aminoethoxyvinyl)glycine (AVG),L-aminooxyphenylpropionic acid (L-AOPP), aminooxyacetic acid (AOA) and2-aminooxyisobutyric acid (AOIBA) are known (Patent Literature 1).

CITATION LIST Patent Literature

-   Patent Literature 1: International Publication WO2008-150031

SUMMARY OF INVENTION

L-AOPP known as an auxin biosynthesis inhibitor has low stability.Therefore, even if it is used in a medium, a growth inhibitory effect onplants is rarely observed. In addition, L-AOPP has so far been long usedas an inhibitor of phenylalanineammonia-lyase (PAL). Since L-AOPPinhibits PAL, synthesis of important secondary metabolites, such asanthocyanin, flavonoid and lignin, is inhibited and synthesis of a planthormone, i.e., salicylic acid, is further inhibited. Such side effectsoccur.

Accordingly, an object of the present invention is to provide an auxinbiosynthesis inhibitor superior to L-AOPP.

The present inventors conducted intensive studies. As a result, theyfound that by modifying a phenyl group, a carboxyl group and an aminooxygroup of L-AOPP the substrate specificity, permeability and stability ofthe resulting compound can be improved and the side effects can bereduced.

To describe more specifically, the present invention include thefollowings.

(1) A compound represented by general formula (I):

wherein,

R¹ is a substituted or unsubstituted aryl group (provided thatunsubstituted phenyl is excluded), a substituted or unsubstitutedheteroaryl group, a substituted or unsubstituted heterocycloalkyl group,a substituted or unsubstituted aryl-fused cycloalkyl group, or asubstituted or unsubstituted aryl-fused heterocycloalkyl group;

R² is hydrogen or a substituted or unsubstituted alkyl group;

R³ and R⁴, which are the same or different, are each hydrogen or asubstituted or unsubstituted acyl group, or R³ and R⁴ together form asubstituted or unsubstituted alkylidene group or, together with anitrogen atom to which R³ and R⁴ are bound, form a substituted orunsubstituted cyclic imide group;

R⁵ is hydrogen or a substituted or unsubstituted alkyl; and

X is O, NH or CH₂,

or a salt or solvate thereof.

(2) The compound, or a salt or solvate thereof according to (1), wherein

R¹ is chlorophenyl, bromophenyl, biphenyl, phenoxyphenyl,4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl, dichlorophenyl,6-methoxy-2-naphthyl, naphthyl or quinolinyl;

R² is C₁₋₆ alkyl;

R³ is hydrogen and R⁴ is acetyl or benzoyl, or R³ and R⁴ together formpropan-2-ylidene or, together with a nitrogen atom to which R³ and R⁴are bound, form phthalimide or succinimide;

R⁵ is hydrogen; and

X is O.

(3) An auxin biosynthesis inhibitor comprising a compound represented bygeneral formula (I′):

wherein,

R^(1′) is a substituted or unsubstituted aryl group, a substituted orunsubstituted heteroaryl group, a substituted or unsubstitutedheterocycloalkyl group, a substituted or unsubstituted aryl-fusedcycloalkyl group, or a substituted or unsubstituted aryl-fusedheterocycloalkyl group;

R^(2′) is hydrogen or a substituted or unsubstituted alkyl group;

R^(3′) and R^(4′), which are the same or different, are each hydrogen ora substituted or unsubstituted acyl group, or R^(3′) and R^(4′) togetherform a substituted or unsubstituted alkylidene group or, together with anitrogen atom to which R^(3′) and R^(4′) are bound, form a substitutedor unsubstituted cyclic imide group;

R^(5′) is hydrogen or a substituted or unsubstituted alkyl; and

X′ is O, NH or CH₂

provided that when R^(1′) is unsubstituted phenyl, R^(2′), R^(3′) andR^(4′) are not hydrogen at the same time), or

a salt or solvate thereof.

(4) The auxin biosynthesis inhibitor according to (3), wherein

R^(1′) is chlorophenyl, bromophenyl, biphenyl, phenoxyphenyl,4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl, dichlorophenyl,6-methoxy-2-naphthyl, naphthyl or quinolinyl;

R^(2′) is C₁₋₆ alkyl;

R^(3′) is hydrogen and R^(4′) is acetyl or benzoyl, or R^(3′) and R^(4′)together form propan-2-ylidene or, together with a nitrogen atom towhich R^(3′) and R^(4′) are bound, form phthalimide or succinimide;

R^(5′) is hydrogen; and

X′ is O.

(5) A tryptophan aminotransferase inhibitor comprising a compoundrepresented by general formula (I″):

wherein,

R^(1″) is a substituted or unsubstituted aryl group (provided thatunsubstituted phenyl is excluded), a substituted or unsubstitutedheteroaryl group, a substituted or unsubstituted heterocycloalkyl group,a substituted or unsubstituted aryl-fused cycloalkyl group, or asubstituted or unsubstituted aryl-fused heterocycloalkyl group;

R^(2″) is hydrogen;

R^(3″) and R^(4″) are each hydrogen;

R^(5″) is hydrogen; and

X″ is O, NH or CH₂, or

a salt, solvate or a prodrug thereof.

(6) The tryptophan aminotransferase inhibitor according to (5), wherein

R^(1″) is bromophenyl, biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,6-methoxy-2-naphthyl, naphthyl or quinolinyl;

R^(2″) is hydrogen;

R^(3″) and R^(4″) are each hydrogen;

R^(5″) is hydrogen; and

X″ is O, NH or CH₂.

(7) A method for inhibiting biosynthesis of auxin in a plant, comprisingapplying the auxin biosynthesis inhibitor according to (3) or (4) to theplant.

(8) A method for inhibiting tryptophan aminotransferase in a plant,comprising applying the tryptophan aminotransferase inhibitor accordingto (5) or (6) to the plant.

(9) A method for inhibiting tryptophan aminotransferase, comprisingbringing the tryptophan aminotransferase inhibitor according to (5) or(6) into contact with the tryptophan aminotransferase in vitro.

(10) A method for regulating growth of a plant, comprising applying thecompound according to (1) or (2), the auxin biosynthesis inhibitoraccording to (3) or (4), or the tryptophan aminotransferase inhibitoraccording to (5) or (6) to the plant.

(11) A method for weeding a plant, comprising applying the compoundaccording to (1) or (2), the auxin biosynthesis inhibitor according to(3) or (4), or the tryptophan aminotransferase inhibitor according to(5) or (6) to the plant.

The specification incorporates the content of the specification and/orthe drawings of JP Patent Application No. 2011-43277 upon which thepriority right of the present application is based.

BRIEF DESCRIPTION OF DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof necessary fee.

FIG. 1 shows auxin biosynthetic pathways.

FIG. 2-1 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-2 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-3 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-4 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-5 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-6 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-7 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-8 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-9 shows synthetic pathways of the compounds of the presentinvention.

FIG. 2-10 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-11 shows a synthetic pathway of the compound of the presentinvention.

FIG. 2-12 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-13 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-14 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-15 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-16 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-17 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-18 shows a synthetic pathway of the compounds of the presentinvention.

FIG. 2-19 shows a synthetic pathway of the compound of the presentinvention.

FIG. 3 shows endogenous amounts (relative value) of IAA in arabidopsistreated with the compound of the present invention.

FIG. 4-1 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-2 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-3 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-4 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-5 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-6 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-7 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 4-8 shows morphology of arabidopsis cultured with the compound ofthe present invention.

FIG. 5-1 shows morphology of arabidopsis cultured with the compound ofthe present invention and IAA.

FIG. 5-2 shows morphology of arabidopsis cultured with the compound ofthe present invention and IAA.

FIG. 5-3 shows morphology of arabidopsis cultured with the compound ofthe present invention and IAA.

FIG. 5-4 shows morphology of arabidopsis cultured with the compound ofthe present invention and IAA.

FIG. 6-1 shows morphology of tobacco cultured with the compound of thepresent invention.

FIG. 6-2 shows morphology of tobacco cultured with the compound of thepresent invention.

FIG. 6-3 shows morphology of tobacco cultured with the compound of thepresent invention.

FIG. 6-4 shows morphology of tobacco cultured with the compound of thepresent invention.

FIG. 7 shows morphology of lettuce cultured with the compound of thepresent invention.

FIG. 8 shows the results of TAA1 inhibitory test.

FIG. 9 shows the results of PAL2 inhibitory test.

FIG. 10 shows morphology of rice treated with the compound of thepresent invention.

FIG. 11 shows morphology of tomato treated with the compound of thepresent invention.

FIG. 12 shows morphology of Physcomitrella patens subsp. Patens treatedwith the compound of the present invention.

DESCRIPTION OF EMBODIMENTS

Now, the present invention will be more specifically described below.

1. Compound

The present invention relates to a compound represented by generalformula (I):

wherein, R¹ to R⁵ and X are the same as defined below, or

a salt or solvate thereof.

If the compound of the present invention has a single or a plurality ofchiral centers, individual enantiomers and diastereomers as well asracemates are included in the present invention. The same applies to theauxin biosynthesis inhibitor and tryptophan aminotransferase inhibitordescribed below.

In general formula (I), R¹ is a substituted or unsubstituted aryl group(provided that unsubstituted phenyl is excluded), a substituted orunsubstituted heteroaryl group, a substituted or unsubstitutedheterocycloalkyl group, a substituted or unsubstituted aryl-fusedcycloalkyl group, or a substituted or unsubstituted aryl-fusedheterocycloalkyl group. Preferably, R¹ is a substituted or unsubstitutedaryl group (provided that unsubstituted phenyl is excluded), asubstituted or unsubstituted heteroaryl group or a substituted orunsubstituted heterocycloalkyl group. More preferably, R¹ is asubstituted aryl group, a substituted or unsubstituted heteroaryl groupor a substituted or unsubstituted heterocycloalkyl group. Particularlypreferably, R¹ is a substituted aryl group or a substituted orunsubstituted heteroaryl group.

Each of the groups represented by R¹ may be substituted withsubstituents such as halogen (for example, fluorine, chlorine, bromine,iodine), an alkyl group (for example, C₁₋₆ alkyl, C₁₋₃ alkyl), ahaloalkyl group (for example, C₁₋₃ haloalkyl, trifluoromethyl), acycloalkyl group (for example, C₃₋₇ cycloalkyl, C₅₋₆ cycloalkyl), analkoxy group (for example, C₁₋₆ alkoxy, C₁₋₃ alkoxy), a haloalkoxy group(for example, C₁₋₆ haloalkoxy, C₁₋₃ haloalkoxy, trifluoromethoxy), anaryl group (for example, C₆₋₁₀ aryl, phenyl), an aryl-substituted phenylgroup (for example, C₆₋₁₀ aryl-substituted phenyl, biphenyl), aheteroaryl group (for example, thiophene), an aryl-substitutedheteroaryl group (for example, C₆₋₁₀ aryl-substituted heteroaryl,phenylthiophene), an aryloxy group (for example, C₆₋₁₀ aryloxy,phenyloxy), an oxo group, an amino group, a nitro group and a cyanogroup.

Examples of the aryl group represented by R¹ include C₆₋₁₄ aryl andC₆₋₁₀ aryl. Particularly, chlorophenyl, bromophenyl, biphenyl,phenoxyphenyl, 4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl,dichlorophenyl, 6-methoxy-2-naphthyl, 4-(4′-chlorophenyl)phenyl andnaphthyl are preferable. Particularly, naphthyl is preferable.

Examples of the heteroaryl group represented by R¹ include a 5 to 10membered heteroaryl and 5 or 6-membered heteroaryl having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur as ring member(s).Particularly, indolyl, quinolinyl, isoquinolinyl, quinoxalinyl,cinnolinyl, benzothiazolyl, thiazolyl, benzoxazolyl and benzothiopheneare preferable.

Examples of the heterocycloalkyl group represented by R¹ include a 5 to10 membered heterocycloalkyl and 5 or 6-membered heterocycloalkyl having1 to 3 hetero atoms selected from nitrogen, oxygen and sulfur as ringmember(s). Particularly, phenylpiperidinyl is preferable.

Examples of the aryl-fused cycloalkyl group represented by R¹ includegroups in which phenyl is fused to C₅₋₆ cycloalkyl. Particularly, groupshaving a structure shown below are preferable:

Examples of the aryl-fused heterocycloalkyl group represented by R¹include groups in which phenyl is fused to a 5 or 6-memberedheterocycloalkyl having 1 to 3 hetero atoms selected from nitrogen,oxygen and sulfur as ring member(s). Particularly, groups having astructure shown below are preferable:

In general formula (I), R² is hydrogen or a substituted or unsubstitutedalkyl group. Preferably, R² is a substituted or unsubstituted alkylgroup.

The alkyl group represented by R² may be substituted with halogen (forexample, fluorine, chlorine, bromine, iodine), a cycloalkyl group (forexample, C₃₋₇ cycloalkyl, C₅₋₆ cycloalkyl), an alkoxy group (forexample, C₁₋₆ alkoxy, C₁₋₃ alkoxy).

Examples of the alkyl group represented by R² include C₁₋₆ alkyl andC₁₋₄ alkyl. Particularly, methyl, ethyl and butyl are preferable.

In general formula (I), R³ and R⁴, which are the same or different, areeach hydrogen or a substituted or unsubstituted acyl group, or R³ and R⁴together form a substituted or unsubstituted alkylidene group or,together with a nitrogen atom to which R³ and R⁴ are bound, form asubstituted or unsubstituted cyclic imide group. Preferably, R³ ishydrogen and R⁴ is a substituted or unsubstituted acyl group, or R³ andR⁴ together form a substituted or unsubstituted alkylidene group or,together with a nitrogen atom to which R³ and R⁴ are bound, form asubstituted or unsubstituted cyclic imide group.

Examples of the acyl group represented by R³ and R⁴ may be substitutedwith substituents such as halogen (for example, fluorine, chlorine,bromine, iodine), a cycloalkyl group (for example, C₃₋₇ cycloalkyl, C₅₋₆cycloalkyl), an alkoxy group (for example, C₁₋₆ alkoxy, C₁₋₃ alkoxy) anda carboxyl group. Furthermore, if the acyl group has an aromatic moiety,the aromatic moiety may be further substituted with substituents such asan alkyl group (for example, C₁₋₆ alkyl, C₁₋₃ alkyl), a haloalkyl group(for example, C₁₋₃ haloalkyl, trifluoromethyl), an amino group, a nitrogroup and a cyano group.

The alkylidene group that R³ and R⁴ form may be substituted withsubstituents such as halogen (for example, fluorine, chlorine, bromine,iodine), a cycloalkyl group (for example, C₃₋₇ cycloalkyl, C₅₋₆cycloalkyl) and an alkoxy group (for example, C₁₋₆ alkoxy, C₁₋₃ alkoxy).

The cyclic imide group that R³ and R⁴ form, together with a nitrogenatom, may be substituted with substituents such as halogen (for example,fluorine, chlorine, bromine, iodine), an alkyl group (for example, C₁₋₆alkyl, C₁₋₃ alkyl), a haloalkyl group (for example, C₁₋₃ haloalkyl,trifluoromethyl), a cycloalkyl group (for example, C₃₋₇ cycloalkyl, C₅₋₆cycloalkyl) and an alkoxy group (for example, C₁₋₆ alkoxy, C₁₋₃ alkoxy).

Examples of the acyl group represented by R³ and R⁴ include C₂₋₁₁ acyland C₂₋₇ acyl. Particularly, acetyl and benzoyl are preferable.

Examples of the alkylidene group that R³ and R⁴ form include C₃₋₁₀alkylidene and C₃₋₆ alkylidene. Particularly, propan-2-ylidene ispreferable.

Examples of the cyclic imide group that R³ and R⁴ form, together withnitrogen atom include C₄₋₈ cyclic imide. Particularly, phthalimide andsuccinimide are preferable.

In general formula (I), R⁵ is hydrogen or a substituted or unsubstitutedalkyl. Preferably, R⁵ is hydrogen.

The alkyl group represented by R⁵ may be substituted with substituentssuch as halogen (for example, fluorine, chlorine, bromine, iodine), acycloalkyl group (for example, C₃₋₇ cycloalkyl, C₅₋₆ cycloalkyl), and analkoxy group (for example, C₁₋₆ alkoxy and C₁₋₃ alkoxy).

Examples of the alkyl group represented by R⁵ include C₁₋₆ alkyl andC₁₋₃ alkyl. As the alkyl group, particularly methyl is preferable.

In general formula (I), X is O, CH₂ or NH. Preferably, X is O or NH.Particularly preferably, X is O.

The compounds represented by general formula (I) include compounds inwhich R¹ to R⁵ and X satisfying the aforementioned definitions arearbitrarily employed in combination. Although it is not particularlylimited, in view of higher stability, a compound in which R² to R⁴ arenot hydrogen at the same time, is preferable. For example, a compound,in which R² is hydrogen; R³ is hydrogen and R⁴ is a substituted orunsubstituted acyl group, or R³ and R⁴ together form a substituted orunsubstituted alkylidene group or, together with a nitrogen atom towhich R³ and R⁴ are bound, form a substituted or unsubstituted cyclicimide group, is preferable. Particularly a compound in which R² is asubstituted or unsubstituted alkyl group; R³ is hydrogen and R⁴ is asubstituted or unsubstituted acyl group, or R³ and R⁴ together form asubstituted or unsubstituted alkylidene group or, together with anitrogen atom to which R³ and R⁴ are bound, form a substituted orunsubstituted cyclic imide group is particularly preferable.

The salts of a compound represented by general formula (I) are notparticularly limited as long as they do not have a negative effect uponthe activity of the compound. Examples thereof include salts of analkaline metal (e.g., a lithium salt, a sodium salt, a potassium salt),salts of an alkaline earth metal (e.g., a magnesium salt, a calciumsalt), and acid addition salts (a inorganic acid salt or an organicsalt, for example, a hydrochloride, a hydrobromate, a nitrate, asulfate, a phosphate, an acetate, a phenyl acetate, propionate,butyrate, valerate, maleate, acrylate, fumarate, malate, tartrate,citrate, salicylate, lactate, phthalate, oxalate, succinate, benzoate,formate, ascorbate, palmitate, oleate, benzene sulfonate and tosylate)

The solvates of a compound represented by general formula (I) are notparticularly limited as long as they do not have a negative effect uponthe activity of the compound. Examples thereof include solvates with anorganic solvent such as methanol, ethanol, isopropanol,dimethylsulfoxide (DMSO), acetic acid, ethanolamine and ethyl acetate,and hydrates with water.

An embodiment of the present invention is directed to a compoundrepresented by general formula (I) where R¹ is a substituted orunsubstituted aryl group (provided that unsubstituted phenyl isexcluded), a substituted or unsubstituted heteroaryl group or asubstituted or unsubstituted heterocycloalkyl group; R² is hydrogen or asubstituted or unsubstituted alkyl group; R³ and R⁴, which are the sameor different, are each hydrogen or a substituted or unsubstituted acylgroup, or R³ and R⁴ together form a substituted or unsubstitutedalkylidene group or, together with a nitrogen atom to which R³ and R⁴are bound, form a substituted or unsubstituted cyclic imide group; R⁵ ishydrogen or a substituted or unsubstituted alkyl; and X is O or NH; or asalt or solvate thereof.

A preferable embodiment of the present invention is directed to acompound represented by general formula (I) where R¹ is a substitutedaryl group, a substituted or unsubstituted heteroaryl group or asubstituted or unsubstituted heterocycloalkyl group; R² is hydrogen or asubstituted or unsubstituted alkyl group; R³ and R⁴, which are the sameor different, are each hydrogen or a substituted or unsubstituted acylgroup, or R³ and R⁴ together form a substituted or unsubstitutedalkylidene group or, together with a nitrogen atom to which R³ and R⁴are bound, form a substituted or unsubstituted cyclic imide group; R⁵ ishydrogen or a substituted or unsubstituted alkyl; and X is O or NH; or asalt or solvate thereof.

Specific examples of the preferable embodiment include a compoundrepresented by general formula (I) where R¹ is chlorophenyl,bromophenyl, biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,4-chloro-2-methylphenyl, dichlorophenyl, 6-methoxy-2-naphthyl, naphthylor quinolinyl; R² is hydrogen or C₁₋₆ alkyl; R³ and R⁴, which are thesame or different, are each hydrogen, acetyl or benzoyl or R³ and R⁴together form propan-2-ylidene or, together with a nitrogen atom towhich R³ and R⁴ are bound, form phthalimide or succinimide; R⁵ ishydrogen or methyl; and X is O or NH; or a salt or solvate thereof.

A further preferable embodiment of the present invention is directed toa compound represented by general formula (I) where R¹ is substitutedaryl group or a substituted or unsubstituted heteroaryl group; R² is asubstituted or unsubstituted alkyl group; R³ is hydrogen and R⁴ is asubstituted or unsubstituted acyl group, or R³ and R⁴ together form asubstituted or unsubstituted alkylidene group or, together with anitrogen atom to which R³ and R⁴ are bound, form a substituted orunsubstituted cyclic imide group; R⁵ is hydrogen; and X is O or NH; or asalt or solvate thereof.

Specific examples of the further preferable embodiment include acompound represented by general formula (I) where R¹ is chlorophenyl,bromophenyl, biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,4-chloro-2-methylphenyl, dichlorophenyl, 6-methoxy-2-naphthyl, naphthylor quinolinyl; R² is C₁₋₆ alkyl; R³ is hydrogen and R⁴ is acetyl orbenzoyl or R³ and R⁴ together form propan-2-ylidene or, together with anitrogen atom to which R³ and R⁴ are bound, form phthalimide orsuccinimide; R⁵ is hydrogen; and X is O or NH; or a salt or solvatethereof.

A particularly preferable embodiment of the present invention isdirected to a compound represented by general formula (I) wherein R¹ issubstituted aryl group or a substituted or unsubstituted heteroarylgroup; R² is a substituted or unsubstituted alkyl group; R³ is hydrogenand R⁴ is a substituted or unsubstituted acyl group, or R³ and R⁴together form a substituted or unsubstituted alkylidene group or,together with a nitrogen atom to which R³ and R⁴ are bound, form asubstituted or unsubstituted cyclic imide group; R⁵ is hydrogen; and Xis O; or a salt or solvate thereof.

Specific examples of the particularly preferable embodiment include acompound represented by general formula (I) where R¹ is chlorophenyl,bromophenyl, biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,4-chloro-2-methylphenyl, dichlorophenyl, 6-methoxy-2-naphthyl, naphthylor quinolinyl; R² is C₁₋₆ alkyl; R³ is hydrogen and R⁴ is acetyl orbenzoyl or R³ and R⁴ together form propan-2-ylidene or, together with anitrogen atom to which R³ and R⁴ are bound, form phthalimide orsuccinimide; R⁵ is hydrogen; and X is O; a salt or solvate thereof.

2. Auxin Biosynthesis Inhibitor

The present invention further relates to an auxin biosynthesis inhibitorcomprising a compound represented by general formula (I′):

wherein, R^(1′) to R^(5′) and X′ are the same as defined below, or

a salt or solvate thereof.

In general formula (I′), R^(1′) is a substituted or unsubstituted arylgroup, a substituted or unsubstituted heteroaryl group, a substituted orunsubstituted heterocycloalkyl group, a substituted or unsubstitutedaryl-fused cycloalkyl group, or a substituted or unsubstitutedaryl-fused heterocycloalkyl group. Preferably, R^(1′) is a substitutedor unsubstituted aryl group, a substituted or unsubstituted heteroarylgroup or a substituted or unsubstituted heterocycloalkyl group.Particularly preferably, R^(1′) is a substituted aryl group or asubstituted or unsubstituted heteroaryl group.

In general formula (I′), R^(2′) is hydrogen or a substituted orunsubstituted alkyl group. Preferably, R^(2′) is a substituted orunsubstituted alkyl group.

In general formula (I′), R^(3′) and R^(4′), which are the same ordifferent, are each hydrogen or a substituted or unsubstituted acylgroup, or R^(3′) and R^(4′) together form a substituted or unsubstitutedalkylidene group or, together with a nitrogen atom to which R^(3′) andR^(4′) are bound, form a substituted or unsubstituted cyclic imidegroup. Preferably, R^(3′) is hydrogen and R^(4′) is a substituted orunsubstituted acyl group, or R^(3′) and R^(4′) together form asubstituted or unsubstituted alkylidene group or, together with anitrogen atom to which R^(3′) and R^(4′) are bound, form a substitutedor unsubstituted cyclic imide group.

In general formula (I′), R^(5′) is hydrogen or a substituted orunsubstituted alkyl. Preferably, R^(5′) is hydrogen.

In general formula (I′), X′ is O, CH₂ or NH. Preferably, X′ is O or NH.Particularly preferably, X′ is O.

Specific examples of R^(1′) to R^(5′) of general formula (I′) andspecific examples of substituents which may substitute for the groups ofR^(1′) to R^(5′) are the same as described with respect to R¹ to R⁵ ofgeneral formula (I). Note that R^(1′) of general formula (I′) may beunsubstituted phenyl; however in this case, R^(2′) to R^(4′) are nothydrogen as the same time.

The compounds represented by general formula (I′) include compounds inwhich R^(1′) to R^(5′) and X′ satisfying the aforementioned definitionsare arbitrarily employed in combination. Although it is not particularlylimited, in view of high stability, a compound in which R^(2′) to R^(4′)are not hydrogen at the same time, is preferable. For example, acompound, in which R^(2′) is hydrogen; R^(3′) is hydrogen and R^(4′) isa substituted or unsubstituted acyl group, or R^(3′) and R^(4′) togetherform a substituted or unsubstituted alkylidene group or, together with anitrogen atom to which R^(3′) and R^(4′) are bound, form a substitutedor unsubstituted cyclic imide group is preferable. Particularly, acompound, in which R^(2′) is a substituted or unsubstituted alkyl group;R^(3′) is hydrogen and R^(4′) is a substituted or unsubstituted acylgroup, or R^(3′) and R^(4′) together form a substituted or unsubstitutedalkylidene group or, together with a nitrogen atom to which R^(3′) andR^(4′) are bound, form a substituted or unsubstituted cyclic imide groupis particularly preferable.

Specific examples of the salt and solvate of a compound represented bygeneral formula (I′) are the same as described with respect to the saltand solvate of a compound represented by general formula (I).

A preferable embodiment of the present invention is directed to an auxinbiosynthesis inhibitor containing a compound represented by generalformula (I′) where R^(1′) is a substituted or unsubstituted aryl group,a substituted or unsubstituted heteroaryl group or a substituted orunsubstituted heterocycloalkyl group; R^(2′) is hydrogen or asubstituted or unsubstituted alkyl group; R^(3′) and R^(4′), which arethe same or different, are each hydrogen or a substituted orunsubstituted acyl group, or R^(3′) and R^(4′) together form asubstituted or unsubstituted alkylidene group or, together with anitrogen atom to which R^(3′) and R^(4′) are bound, form a substitutedor unsubstituted cyclic imide group; R^(5′) is hydrogen or a substitutedor unsubstituted alkyl; and X′ is O or NH (provided that when R′ isunsubstituted phenyl, R^(2′), R^(3′) and R^(4′) are not hydrogen at thesame time); or a salt or solvate thereof. The auxin biosynthesisinhibitor of the embodiment has an auxin biosynthesis inhibitoryactivity equal to or more than that of L-AOPP and high stability.

Specific examples of the preferable embodiment include an auxinbiosynthesis inhibitor containing a compound represented by generalformula (I′) where R^(1′) is phenyl, chlorophenyl, bromophenyl,biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,4-chloro-2-methylphenyl, dichlorophenyl, 6-methoxy-2-naphthyl, naphthylor quinolinyl; R^(2′) is hydrogen or C₁₋₆ alkyl; R^(3′) and R^(4′),which are the same or different, each are hydrogen, acetyl or benzoyl orR^(3′) and R^(4′) together form propan-2-ylidene or, together with anitrogen atom to which R^(3′) and R^(4′) are bound, form phthalimide orsuccinimide; R^(5′) is hydrogen or methyl; and X′ is O or NH (providedthat when R^(1′) is unsubstituted phenyl, R^(2′), R^(3′) and R^(4′) arenot hydrogen at the same time); or a salt or solvate thereof.

A further preferable embodiment of the present invention is directed toan auxin biosynthesis inhibitor containing a compound represented bygeneral formula (I′) where R^(1′) is a substituted or unsubstituted arylgroup or a substituted or unsubstituted heteroaryl group; R^(2′) is asubstituted or unsubstituted alkyl group; R^(3′) is hydrogen and R^(4′)is a substituted or unsubstituted acyl group, or R^(3′) and R^(4′)together form a substituted or unsubstituted alkylidene group or,together with a nitrogen atom to which R^(3′) and R^(4′) are bound, forma substituted or unsubstituted cyclic imide group; R^(5′) is hydrogen;and X′ is O or NH; or a salt or solvate thereof. The auxin biosynthesisinhibitor of the embodiment has an auxin biosynthesis inhibitoryactivity equal to or more than that of L-AOPP and extremely highstability.

Specific examples of the further preferable embodiment include an auxinbiosynthesis inhibitor containing a compound represented by generalformula (I′) where R^(1′) is phenyl, chlorophenyl, bromophenyl,biphenyl, phenoxyphenyl, 4-chloro-3-methylphenyl,4-chloro-2-methylphenyl, dichlorophenyl, 6-methoxy-2-naphthyl, naphthylor quinolinyl; R^(2′) is C₁₋₆ alkyl; R^(3′) is hydrogen and R^(4′) isacetyl or benzoyl or R^(3′) and R^(4′) together form propan-2-ylideneor, together with a nitrogen atom to which R^(3′) and R^(4′) are bound,form phthalimide or succinimide; R^(5′) is hydrogen; and X is O or NH;or a salt or solvate thereof.

The particularly preferable embodiment of the present invention isdirected to an auxin biosynthesis inhibitor containing a compoundrepresented by general formula (I′) where R^(1′) is substituted arylgroup or a substituted or unsubstituted heteroaryl group; R^(2′) is asubstituted or unsubstituted alkyl group; R^(3′) is hydrogen and R^(4′)is a substituted or unsubstituted acyl group, or R^(3′) and R^(4′)together form a substituted or unsubstituted alkylidene group or,together with a nitrogen atom to which R^(3′) and R^(4′) are bound, forma substituted or unsubstituted cyclic imide group; R^(5′) is hydrogen;and X′ is O; or a salt or solvate thereof. The auxin biosynthesisinhibitor of the embodiment has an auxin biosynthesis inhibitoryactivity superior to that of L-AOPP and extremely high stability.

Specific examples of the particularly preferable embodiment include anauxin biosynthesis inhibitor containing a compound represented bygeneral formula (I′) where R¹ is chlorophenyl, bromophenyl, biphenyl,phenoxyphenyl, 4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl,dichlorophenyl, 6-methoxy-2-naphthyl, naphthyl or quinolinyl; R^(2′) isC₁₋₆ alkyl; R^(3′) is hydrogen and R^(4′) is acetyl or benzoyl or R^(3′)and R^(4′) together form a substituted or unsubstituted propan-2-ylideneor, together with a nitrogen atom to which R^(3′) and R^(4′) are bound,form phthalimide or succinimide; R^(5′) is hydrogen; and X′ is O; or asalt or solvate thereof.

3. Tryptophan Aminotransferase Inhibitor

The present invention further relates to a tryptophan aminotransferaseinhibitor comprising a compound represented by general formula (I″):

wherein, R^(1″) to R^(5″) and X″ are the same as defined below, or

a salt, solvate or a prodrug thereof.

In general formula (I″), R^(1″) is a substituted or unsubstituted arylgroup (provided that unsubstituted phenyl is excluded), a substituted orunsubstituted heteroaryl group, a substituted or unsubstitutedheterocycloalkyl group, a substituted or unsubstituted aryl-fusedcycloalkyl group, or a substituted or unsubstituted aryl-fusedheterocycloalkyl group. Preferably, R^(1″) is a substituted aryl groupor a substituted or unsubstituted heteroaryl group.

R^(2″) to R^(5″) each are hydrogen.

X″ is O, NH or CH₂. Preferably, X″ is O or NH. Particularly preferably,X″ is O.

Specific examples of R^(1″) of general formula (I″), and specificexamples of substituents that may be substituted for the group of R^(1″)are the same as described with respect to R¹ of general formula (I).

Specific examples of the salt and solvate of a compound represented bygeneral formula (I″) are the same as described with respect to the saltand solvate of a compound represented by general formula (I).

Examples of a prodrug of a compound represented by general formula (I″)include a prodrug in which the carboxyl group (COOR^(2″)) and aminogroup (NR^(3″)R^(4″)) in general formula (I″) are protected withprotecting groups, which are to be converted to a free carboxylic acidand free amine, respectively in a plant.

Examples of the carboxyl group protected include an ester, a thioester,an amide, and a nitrile. Examples thereof include a C₁₋₆ alkyl ester, aC₁₋₄ alkyl ester, a C₁₋₆ alkylthio ester, a C₁₋₄ alkylthio ester, a—CONR^(a) ₂ (R^(a) each independently represent e.g., hydrogen, C₁₋₆alkyl, C₁₋₃ alkyl).

Examples of the amino group protected include an amide, an imide and animine. Examples thereof include —NHCOR^(b) (R^(b) is e.g., C₁₋₃ alkyl(preferably methyl), aryl (preferably phenyl)), a cyclic imide(preferably phthalimide, succinimide), —N═CR^(c) ₂ (R^(c) eachindependently represent e.g., C₁₋₃ alkyl).

Either one or both of the carboxyl group and amino group may beprotected.

An embodiment of the present invention is directed to a tryptophanaminotransferase inhibitor containing a compound represented by generalformula (I″) where R^(1″) is substituted aryl group or a substituted orunsubstituted heteroaryl group; R^(2″) to R^(5″) each are hydrogen; andX″ is O, NH or CH₂ (preferably, X″ is O); or a salt, solvate or aprodrug thereof.

Examples of the embodiment include a tryptophan aminotransferaseinhibitor containing a compound represented by general formula (I″)where R^(1″) is chlorophenyl, bromophenyl, biphenyl, phenoxyphenyl,4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl, dichlorophenyl,6-methoxy-2-naphthyl, naphthyl or quinolinyl; R^(2″) to R^(5″) each arehydrogen; and X″ is O, NH or CH₂ (preferably, X″ is O); or a salt,solvate or a prodrug thereof. The tryptophan aminotransferase inhibitorof the embodiment has an enzyme inhibitory activity equal to or morethan that of L-AOPP.

Preferable examples of the embodiment include tryptophanaminotransferase inhibitor containing a compound represented by generalformula (I″) where R^(1″) is 4-chlorophenyl, 3-chlorophenyl, biphenyl,4-chloro-3-methylphenyl or naphthyl; R^(2″) to R^(5″) each are hydrogen;and X″ is O; or a salt, solvate or a prodrug thereof. The tryptophanaminotransferase inhibitor of the embodiment has enzyme inhibitoryactivity superior to that of L-AOPP.

Preferable examples of the embodiment include a tryptophanaminotransferase inhibitor containing a compound represented by generalformula (I″) where R^(1″) is bromophenyl, biphenyl, phenoxyphenyl,4-chloro-3-methylphenyl, 6-methoxy-2-naphthyl, naphthyl or quinolinyl;R^(2″) to R^(5″) each are hydrogen; and X″ is O; or a salt, solvate or aprodrug thereof. The tryptophan aminotransferase inhibitor of theembodiment has enzyme inhibitory activity equal to or more than that ofL-AOPP and further reduced in side effect (PAL inhibitory activity).

Particularly preferable examples of the embodiment include a tryptophanaminotransferase inhibitor containing a compound represented by generalformula (I″) where R^(1″) is biphenyl, 4-chloro-3-methylphenyl ornaphthyl; R^(2″) to R^(5″) each are hydrogen; and X″ is O; or a salt,solvate or a prodrug thereof. The tryptophan aminotransferase inhibitorof the embodiment has enzyme inhibitory activity superior to that ofL-AOPP and further reduced in side effect (PAL inhibitory activity).

4. Use

The compound of the present invention can be used for inhibitingbiosynthesis of auxin, inhibiting tryptophan aminotransferase in vivo(in a plant) and in vitro, and regulating growth of a plant. Ininhibiting tryptophan aminotransferase in vitro, an inhibitor, which isnot in the form of a prodrug, is preferably used.

The type of plant is not particularly limited as long as the plantbiologically synthesizes auxin and as long as the plant has tryptophanaminotransferase.

A method for applying the compound of the present invention to a plantis not particularly limited as long as the method allows the compound tobe in contact with the plant. Examples thereof include spraying,dusting, atomizing, soaking and spreading.

The phrase “regulating growth of a plant” refers to exerting someinfluence on plant growth and include both a promotive effect and aninhibitory effect. Owing to these effects, the compound of the presentinvention can be used as e.g., a herbicide, a plant growth regulator anda flower keeping agent (freshness-keeping agent).

Now, the present invention will be described in more detail by use ofExamples; however, the technical scope of the present invention is notlimited to these.

1. Synthesis Examples

Compounds were synthesized in accordance with FIG. 2-2.

Synthesis of KOK1158 (Step 1)

The titled compound was synthesized by use of a method described in J.Org. Chem. 2006, 71, 3332-3334. 3-(2-Naphthyl)-D-alanine (5.0 g, 23.2mmol) and sodium bromide (9.7 g, 81.3 mmol) were suspended in 2.5 Msulfuric acid (30 ml) and stirred at 0° C. To the mixture, an aqueoussodium nitrite (2.0 g, 29.0 mmol) solution (10 ml) was added dropwise.After the mixture was stirred at 0° C. for one hour, the temperature ofthe mixture was returned to room temperature and a reaction wasperformed for 6 hours. The reaction solution was extracted with ethylacetate and washed with a saturated aqueous sodium chloride solution.The resultant organic layer was dried over anhydrous sodium sulfate.This was filtered and concentrated under reduced pressure and theresidue was purified by silica gel column chromatography (ethylacetate:acetic acid=100:1) to obtain the titled compound (red-brown oilysubstance: 6.6 g, crude yield 102%) containing impurities.

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.40 (1H, dd, J=14.2, 7.3 Hz), 3.63 (1H,dd, J=14.2, 8.2 Hz), 4.52 (1H, dd, J=8.2, 7.3 Hz), 7.33 (1H, dd, J=8.6,1.7 Hz), 7.40-7.51 (2H, m), 7.69 (1H, s), 7.71-7.86 (3H, m).

Synthesis of KOK1164 (Step 2)

KOK1158 (6.6 g, 23.6 mmol) obtained in Step 1 was dissolved in methanol(50 ml). To this, concentrated sulfuric acid (0.5 ml) was added and themixture was refluxed for 2 hours. The reaction solution was concentratedunder reduced pressure and the residue was purified by silica gel columnchromatography (hexane:ethyl acetate=10:1) to obtain the titled compound(yellow oily substance: 4.1 g, 59%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.40 (1H, dd, J=14.3, 7.3 Hz), 3.63 (1H,dd, J=14.3, 8.6 Hz), 3.71 (3H, s), 4.50 (1H, dd, J=8.6, 7.3 Hz), 7.32(1H, dd, J=8.6, 1.6 Hz), 7.40-7.51 (2H, m), 7.67 (1H, s), 7.72-7.84 (3H,m).

Synthesis of KOK1165 (Step 3)

N-hydroxyphthalimide (2.5 g, 15.4 mmol) and triethylamine (2.1 ml, 15.4mmol) were dissolved in N,N-dimethylformamide (10 ml) and stirred at 60°C. To this, an N,N-dimethylformamide solution (5 ml) containing KOK1164(6.6 g, 23.6 mmol) obtained in Step 2 was added dropwise and stirred at60° C. for 30 minutes. To the reaction solution, water was added and themixture was extracted three times with ethyl acetate, washed three timeswith water and then washed with a saturated aqueous sodium chloridesolution. The resultant organic layer was dried over anhydrous sodiumsulfate, filtered and concentrated under reduced pressure. Thereafter,the residue was purified by silica gel column chromatography(hexane:ethyl acetate=1:1) to obtain the titled compound (light yellowoily substance: 3.9 g, 75%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.41-3.60 (2H, m), 3.72 (3H, s), 5.11(1H, t, J=6.9 Hz), 7.38-7.50 (3H, m), 7.65-7.83 (8H, m).

Synthesis of KOK1168 (Step 4)

KOK1165 (1.3 g, 3.5 mmol) obtained in Step 3 was dissolved inmethanol:1,4-dioxane (1:1.8 ml). To the mixture, hydrazine monohydrate(0.2 g, 4.2 mmol) was added and stirred at room temperature for onehour. A saturated aqueous sodium hydrogen carbonate solution (4 ml) wasadded and concentrated under reduced pressure. To the reaction solution,water was added and the mixture was extracted three times with ethylacetate, washed with a saturated aqueous sodium chloride solution. Theresultant organic layer was dried over anhydrous sodium sulfate,filtered and concentrated under reduced pressure. Thereafter, theresidue was purified by silica gel column chromatography (hexane:ethylacetate=2:1) to obtain the titled compound (colorless oily substance:0.8 g, 100%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.12 (1H, dd, J=14.5, 8.6 Hz), 3.20 (1H,dd, J=14.5, 4.6 Hz), 3.75 (3H, s), 4.51 (1H, dd, J=8.6, 4.6 Hz), 5.67(2H, s), 7.36 (1H, dd, J=8.2, 1.7 Hz), 7.39-7.50 (2H, m), 7.66 (1H, s),7.72-7.84 (3H, m).

Synthesis of KOK1169 (Step 5)

KOK1168 (448 mg, 1.81 mmol) obtained in Step 4 was dissolved in methanol(5 ml). To this, a 2N aqueous sodium hydroxide solution (3.6 ml) wasadded and stirred at room temperature for one hour. To this, 2Nhydrochloric acid was added to adjust pH at 4 and concentrated underreduced pressure. Thereafter, the obtained solid substance was suspendedin water, filtered off and dried under reduced pressure to obtain thetitled compound (white crystal: 391 mg, 93%).

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 3.01 (1H, dd, J=14.5, 8.2 Hz), 3.10(1H, dd, J=14.5, 4.9 Hz), 4.28 (1H, dd, J=8.2, 5.0 Hz), 7.35-7.52 (3H,m), 7.73 (1H, s), 7.77-7.90 (3H, m), 8.35 (2H, brs).

Synthesis of KOK2015 (Step 6)

Acetohydroxamic acid (31 mg, 0.41 mmol) was dissolved inN,N-dimethylformamide (3 ml). To this, sodium hydride (60%) (16 mg, 0.41mmol) was added under ice cooling and stirred for 20 minutes. To themixture, an N,N-dimethylformamide (3 ml) solution containing KOK1164(100 mg, 0.34 mmol) obtained in Step 2 was added dropwise and stirred atroom temperature for 16 hours. To the mixture, water was added and themixture was extracted three times with ethyl acetate, washed three timeswith water and then washed with a saturated aqueous sodium chloridesolution. The organic layer was dried over anhydrous sodium sulfate.This was filtered and concentrated under reduced pressure. Thereafter,the residue was purified by silica gel column chromatography(hexane:ethyl acetate=1:1) to obtain the titled compound (colorless oilysubstance: 79 mg, 81%).

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 1.72 (3H, s), 3.21 (2H, d, J=6.3 Hz),3.61 (3H, s), 4.71 (1H, t, J=6.3 Hz), 7.34-7.54 (3H, m), 7.73-7.92 (4H,m), 11.12 (1H, s).

Synthesis of KOK2016

The titled compound was synthesized from compound KOK1164 in the sameconditions as in Step 3.

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.55 (4H, s), 3.45 (2H, d, J=6.9 Hz),3.71 (3H, s), 5.06 (1H, t, J=6.9 Hz), 7.36-7.50 (3H, m), 7.68-7.83 (4H,m). White crystal.

Synthesis of KOK2011

The titled compound was synthesized from compound KOK1164 in the sameconditions as in Step 6.

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.39 (1H, dd, J=14.8, 6.6 Hz), 3.49 (1H,dd, J=14.8, 5.3 Hz), 3.71 (3H, s), 5.01 (1H, dd, J=6.9, 5.3 Hz),7.32-7.54 (6H, m), 7.62-7.72 (2H, m), 7.72-7.85 (4H, m), 9.17 (1H, s).White crystal.

Synthesis of KOK1168 (Step 7)

To KOK2011 (2.00 g, 5.72 mmol), 2M (2N) hydrochloric acid.methanol (10ml) was added and suspended. The mixture was stirred at room temperaturefor 18 hours. The reaction solution was concentrated under reducedpressure. To the residue, water and ethyl acetate were added. Thereaction solution was adjusted with a 2N aqueous sodium hydroxidesolution at pH4, extracted three times with ethyl acetate and dried overanhydrous sodium sulfate. This was filtered and concentrated underreduced pressure and then the residue was purified by silica gel columnchromatography (hexane:ethyl acetate=2:1) to obtain the titled compound(colorless oily substance: 1.33 g, 95%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.12 (1H, dd, J=14.5, 8.6 Hz), 3.20 (1H,dd, J=14.5, 4.6 Hz), 3.75 (3H, s), 4.51 (1H, dd, J=8.6, 4.6 Hz), 5.67(2H, s), 7.36 (1H, dd, J=8.2, 1.7 Hz), 7.39-7.50 (2H, m), 7.66 (1H, s),7.72-7.84 (3H, m).

Synthesis of KOK1198 (Step 8)

To KOK1168 (60 mg, 0.25 mmol) obtained in Step 4 or 7, acetone (3 ml)was added and stirred at room temperature for 17 hours. The mixture wasconcentrated under reduced pressure to obtain the titled compound (whitecrystal: 70 mg, 100%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.82 (3H, s), 1.87 (3H, s), 3.27 (2H, d,J=6.3 Hz), 3.70 (3H, s), 4.84 (1H, t, J=6.3 Hz), 7.33-7.50 (3H, m), 7.68(1H, s), 7.71-7.84 (3H, m).

Compounds were synthesized in accordance with FIG. 2-3. KOK1192 wassynthesized in the same conditions as used in Step 1, KOK1193 in Step 2,KOK1194 in Step 6, KOK2032 in Step 7, KOK2033 in Step 5, KOK2052 in Step3 and KOK2057 in Step 4.

KOK1193

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.40 (1H, dd, J=14.3, 7.3 Hz), 3.63 (1H,dd, J=14.3, 8.6 Hz), 3.71 (3H, s), 4.50 (1H, dd, J=8.6, 7.3 Hz), 7.32(1H, dd, J=8.6, 1.6 Hz), 7.40-7.51 (2H, m), 7.67 (1H, s), 7.72-7.84 (3H,m). Yellow oily substance.

KOK1194

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.39 (1H, dd, J=14.8, 6.6 Hz), 3.49 (1H,dd, J=14.8, 5.3 Hz), 3.71 (3H, s), 5.01 (1H, dd, J=6.9, 5.3 Hz),7.32-7.54 (6H, m), 7.62-7.72 (2H, m), 7.72-7.85 (4H, m), 9.17 (1H, s).White solid substance.

KOK2032

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.23 (1H, t, J=7.3 Hz), 3.07-3.25 (2H,m), 4.21 (2H, q, J=7.3 Hz), 4.49 (1H, dd, J=8.6, 4.6 Hz), 5.68 (2H,brs), 7.32-7.50 (3H, m), 7.67 (1H, s), 7.72-7.84 (3H, m). Light yellowoily substance.

KOK2033

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 3.01 (1H, dd, J=14.5, 8.2 Hz), 3.10(1H, dd, J=14.5, 4.9 Hz), 4.28 (1H, dd, J=8.2, 5.0 Hz), 7.35-7.52 (3H,m), 7.73 (1H, s), 7.77-7.90 (3H, m), 8.35 (2H, brs). White crystal.

KOK2052

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.41-3.60 (2H, m), 3.72 (3H, s), 5.11(1H, t, J=6.9 Hz), 7.38-7.50 (3H, m), 7.65-7.83 (8H, m). Brown stickyoily substance.

KOK2057

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.12 (1H, dd, J=14.5, 8.6 Hz), 3.20 (1H,dd, J=14.5, 4.6 Hz), 3.75 (3H, s), 4.51 (1H, dd, J=8.6, 4.6 Hz), 5.67(2H, s), 7.36 (1H, dd, J=8.2, 1.7 Hz), 7.39-7.50 (2H, m), 7.66 (1H, s),7.72-7.84 (3H, m). Colorless oily substance.

Compounds were synthesized in accordance with FIG. 2-4. KOK1155 wassynthesized in the same conditions as used in Step 1, KOK1159 in Step 2,KOK1160 in Step 3, KOK1166 in Step 4, KOK1167 in Step 5 and KOK1183 inStep 6. KOK1177 was synthesized in accordance with Step 9 shown below.

KOK1160

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.67 (3H, s), 3.75 (1H, dd, J=14.5, 8.2Hz), 3.92 (1H, dd, J=14.5, 6.3 Hz), 5.11 (1H, dd, J=8.2, 6.3 Hz),7.36-7.63 (4H, m), 7.68-7.90 (6H, m), 8.15 (1H, d, J=8.6 Hz). Lightyellow solid substance.

KOK1166

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.37 (1H, dd, J=14.5, 8.9 Hz), 3.53 (1H,dd, J=14.5, 4.6 Hz), 3.74 (3H, s), 4.57 (1H, dd, J=8.9, 4.6 Hz), 5.64(2H, s), 7.33-7.59 (4H, m), 7.72-7.80 (1H, m), 7.82-7.90 (1H, m), 8.07(1H, d, J=8.2 Hz). Light yellow oily substance.

KOK1167

¹H-NMR (DMSO-d₆, 270 MHz) 5 ppm: 3.28 (1H, dd, J=14.2, 8.2 Hz), 3.41(1H, dd, J=14.2, 4.6 Hz), 4.29 (1H, dd, J=8.2, 4.6 Hz), 7.34-7.47 (2H,m), 7.47-7.62 (2H, m), 7.81 (1H, d, J=7.6 Hz), 7.93 (1H, d, J=7.6 Hz),8.08 (1H, d, J=8.6 Hz), 8.42 (2H, brs). White crystal.

Synthesis of KOK1177 (Step 9)

The titled compound was synthesized in accordance with a methoddescribed in WO2010/041538. 1-Naphthylamine (5.00 g, 34.92 mmol) wasdissolved in methanol (50 ml) and acetone (50 ml) and cooled to 10° C.To this, hydrobromic acid (47 mass %, 12.26 g) (hydrogen bromide: 71.23mmol) was added. The reaction solution was cooled to 2° C. Whilemaintaining the temperature of the reaction solution not to exceed 5°C., an aqueous solution (6 ml) containing sodium nitrite (2.75 g, 39.81mmol) was added dropwise. The resultant mixture was stirred at 2° C. for20 minutes to synthesize a diazonium salt. In a different vessel, methylacrylate (6.01 g, 69.84 mmol), pyridine (8.29 ml, 104.76 mmol) andcopper bromide (I) (0.63 g, 4.40 mmol) were charged and stirred at 47°C. To the mixture solution, a solution containing the diazonium salt wasadded dropwise over 30 minutes. Thereafter, the mixture solution wasfurther stirred at 47° C. for 2 hours and then the solvent wasevaporated. To the obtained residue, ammonia water (28 mass %) wasadded. The solution was extracted three times with ethyl acetate, washedwith water and dried over anhydrous sodium sulfate. This was filteredand concentrated under reduced pressure. Thereafter, the residue waspurified by silica gel column chromatography (hexane:ethyl acetate=10:1)to obtain the titled compound (black oily substance: 4.97 g, crude yield49%) containing impurities.

KOK1183

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.58 (3H, s), 3.62-3.72 (2H, m), 5.06(1H, t, J=6.2 Hz), 7.28-7.58 (7H, m), 7.58-7.70 (2H, m), 7.75 (1H, d,J=7.8 Hz), 7.83 (1H, d, J=7.8 Hz), 7.10 (1H, d, J=8.1 Hz), 9.38 (1H, s).Yellow ocher crystal.

Compounds were synthesized in accordance with FIG. 2-5. KOK2029 wassynthesized in the same conditions as used in Step 3, KOK2030 in Step 4and KOK2031 in Step 5. KOK2019, KOK2025 and KOK2028 were synthesized inaccordance with Steps 10, 11 and 12 shown below, respectively.

Synthesis of KOK2019 (Step 10)

To sodium hydride (60%) (303 mg, 7.57 mmol), tetrahydrofuran (5 ml) wasadded and stirred. To this, a mixture solution of 4-phenoxy benzaldehyde(1.00 g, 5.05 mmol), methyl chloroacetate (657 mg, 6.05 mmol) andtetrahydrofuran (10 ml) was added dropwise and stirred at roomtemperature overnight. The reaction solution was ice-cooled, neutralizedwith 1M sulfuric acid, extracted three times with dichloromethane, driedover anhydrous sodium sulfate, filtered and concentrated under reducedpressure. Thereafter, the residue was purified by silica gel columnchromatography (hexane:ethyl acetate=10:1) to obtain the titled compound(white crystal: 940 mg, 69%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.52 (1H, d, J=1.6 Hz), 3.83 (3H, s),4.08 (1H, d, J=1.6 Hz), 6.94-7.04 (4H, m), 7.08-7.17 (1H, m), 7.20-7.28(2H, m), 7.28-7.40 (2H, m).

Synthesis of KOK2025 (Step 11)

The titled compound was synthesized in accordance with a methoddescribed in Organic Letters 2003, vol. 5, No. 24, 4665-4668. KOK2019(940 mg, 3.48 mmol) obtained in Step 10 and Pd⁰-EnCat® (0.4 mmol/g, 435mg, 0.17 mmol) were dissolved in ethyl acetate (10 ml). To this,triethyl amine (1.93 ml, 13.91 mmol) and formic acid (0.53 ml, 13.91mmol) were added. The reaction solution was stirred under an argonatmosphere at room temperature overnight, and then filtered. Thefiltrate was concentrated under reduced pressure and thereafter theresidue was purified by silica gel column chromatography (hexane:ethylacetate=5:1) to obtain the titled compound (white crystal: 859 mg, 91%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.72 (1H, d, J=5.9 Hz), 2.94 (1H, dd,J=14.2, 6.6 Hz), 3.11 (1H, dd, J=14.2, 4.6 Hz), 3.78 (3H, s), 4.38-4.50(1H, m), 6.88-7.03 (4H, m), 7.03-7.13 (1H, m), 7.13-7.21 (2H, m),7.27-7.37 (2H, m).

Synthesis of KOK2028 (Step 12)

KOK2025 (859 mg, 3.16 mmol) obtained in Step 11 and triphenylphosphine(2.482 g, 9.46 mmol) were dissolved in dichloromethane (6 ml). To this,carbon tetrabromide (1.046 g, 4.73 mmol) was added and stirred at roomtemperature for one hour. To the reaction solution, ice water was added.The reaction solution was extracted three times with dichloromethane.The organic layer was dried over anhydrous sodium sulfate, filtered andconcentrated under reduced pressure. The residue was purified by silicagel column chromatography (hexane:ethyl acetate=20:1) to obtain thetitled compound (white crystal: 937 mg, 89%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.21 (1H, dd, J=14.2, 6.9 Hz), 3.44 (1H,dd, J=14.2, 8.2 Hz), 3.74 (3H, s), 4.37 (1H, dd, J=8.2, 6.9 Hz),6.88-7.03 (4H, m), 7.06-7.20 (3H, m), 7.27-7.38 (2H, m).

KOK2029

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.23-3.41 (2H, m), 3.74 (3H, s), 4.97(1H, t, J=6.9 Hz), 6.90-7.02 (4H, m), 7.04-7.13 (1H, m), 7.23-7.36 (4H,m), 7.70-7.86 (2H, m). Colorless sticky oily substance.

KOK2030

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.88-3.06 (2H, m), 3.75 (3H, s), 4.39(1H, dd, J=8.2, 5.0 Hz), 5.68 (2H, s), 6.88-7.03 (4H, m), 7.03-7.12 (1H,m), 7.12-7.21 (2H, m), 7.26-7.37 (2H, m). White crystal.

KOK2031

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.76-2.97 (2H, m), 4.17 (1H, dd, J=8.2,5.0 Hz), 6.86-7.02 (4H, m), 7.04-7.18 (1H, m), 7.18-7.30 (2H, m),7.30-7.43 (2H, m), 8.38 (2H, brs). White crystal.

Compounds were synthesized in accordance with FIG. 2-6. KOK2014 wassynthesized in the same conditions as used in Step 10, KOK2018 in Step11, KOK2020 in Step 12, KOK2021 in Step 3, KOK2026 in Step 4 and KOK2027in Step 5.

KOK2021

¹H-NMR (CDCl₃, 270 MHz) 5 ppm: 3.30-3.48 (2H, m), 3.74 (3H, s), 5.05(1H, t, J=6.9 Hz), 7.26-7.44 (5H, m), 7.48-7.58 (4H, m), 7.65-7.83 (4H,m). Colorless sticky oily substance.

KOK2026

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.92-3.12 (2H, m), 3.75 (3H, s), 4.44(1H, dd, J=8.5, 4.6 Hz), 5.68 (3H, s), 7.22-7.36 (3H, m), 7.36-7.46 (2H,m), 7.46-7.60 (4H, m). White crystal.

KOK2027

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.88 (1H, dd, J=14.2, 8.2 Hz), 2.98(1H, dd, J=14.2, 4.9 Hz), 4.21 (1H, dd, J=8.2, 4.9 Hz), 7.25-7.39 (3H,m), 7.39-7.50 (2H, m), 7.50-7.68 (4H, m), 8.35 (2H, brs). White crystal.

Compounds were synthesized in accordance with FIG. 2-7. KOK1170 wassynthesized in the same conditions as used in Step 1, KOK1171 in Step 2,KOK1174 in Step 3, KOK1175 in Step 4, KOK1176 in Step 5, KOK1184 in Step9, KOK1185 in Step 3, KOK1186 in Step 4, KOK1187 in Step 5, KOK1173 inStep 9, KOK1178 in Step 3, KOK1179 in Step 4 and KOK1180 in Step 5.

KOK1174

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.22-3.40 (2H, m), 3.74 (3H, s), 4.96(1H, t, J=6.9 Hz), 7.28 (4H, s), 7.70-7.86 (4H, m). White crystal.

KOK1175

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.87-3.06 (2H, m), 3.75 (3H, s), 4.37(1H, dd, J=8.2, 4.6 Hz), 5.67 (2H, s), 7.09-7.18 (2H, m), 7.21-7.29 (2H,m). Colorless oily substance.

KOK1176

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.84 (1H, dd, J=14.2, 8.2 Hz), 2.93(1H, dd, J=14.2, 5.0 Hz), 4.16 (1H, dd, J=8.2, 5.0 Hz), 7.20-7.36 (4H,m), 8.37 (2H, brs). White crystal.

KOK1185

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.28 (1H, dd, J=14.5, 6.6 Hz), 3.35 (1H,dd, J=14.5, 6.9 Hz), 3.75 (3H, s), 4.97 (1H, dd, J=6.9, 6.6 Hz),7.18-7.26 (3H, m), 7.31-7.36 (1H, m), 7.70-7.86 (4H, m). White crystal.

KOK1186

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.93 (1H, dd, J=14.5, 8.6 Hz), 3.02 (1H,dd, J=14.5, 5.0 Hz), 3.76 (3H, s), 4.39 (1H, dd, J=8.6, 5.0 Hz), 5.68(2H, s), 7.04-7.14 (1H, m), 7.16-7.24 (3H, m). Yellow oily substance.

KOK1187

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.86 (1H, dd, J=14.5, 5.0 Hz), 2.96(1H, dd, J=14.5, 8.2 Hz), 4.19 (1H, dd, J=8.2, 5.0 Hz), 7.15-7.34 (4H,m), 8.43 (2H, brs). White crystal.

KOK1178

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.42 (1H, dd, J=14.2, 6.9 Hz), 3.52 (1H,dd, J=14.2, 7.6 Hz), 3.75 (3H, s), 5.07 (1H, dd, J=7.6, 6.9 Hz),7.06-7.27 (2H, m), 7.33-7.44 (2H, m), 7.67-7.85 (4H, m). White crystal.

KOK1179

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.09 (1H, dd, J=14.2, 8.9 Hz), 3.21 (1H,dd, J=14.2, 5.0 Hz), 3.75 (3H, s), 4.51 (1H, dd, J=8.9, 5.0 Hz), 5.66(2H, s), 7.13-7.28 (3H, m), 7.30-7.40 (1H, m). Colorless oily substance.

KOK1180

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.87 (1H, dd, J=14.2, 8.9 Hz), 3.06(1H, dd, J=14.2, 5.0 Hz), 4.23 (1H, dd, J=8.9, 5.0 Hz), 7.17-7.46 (4H,m), 8.45 (2H, brs). White crystal.

Compounds were synthesized in accordance with FIG. 2-8. KOK1152 wassynthesized in the same conditions as used in Step 2, KOK1161 in Step 3,KOK1153 in Step 2, KOK1172 in Step 3, KOK1151 in Step 2, KOK1157 in Step6, and KOK1162 in Step 6.

KOK1172

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 0.85 (3H, t, J=7.3 Hz), 1.15-1.33 (2H,m), 1.45-1.60 (2H, m), 3.24-3.44 (2H, m), 4.10 (2H, t, J=6.5 Hz), 5.00(1H, t, J=7.3 Hz), 7.18-7.37 (5H, m), 7.67-7.85 (4H, m). Colorless oilysubstance.

KOK1157

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.23 (1H, dd, J=14.5, 6.6 Hz), 3.32 (1H,dd, J=14.5, 5.3 Hz), 3.72 (3H, s), 4.93 (1H, dd, J=6.6, 5.3 Hz),7.20-7.55 (8H, m), 7.62-7.71 (2H, m), 7.62-7.71 (2H, m), 9.14 (1H, brs).White crystal.

KOK1162

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.15 (3H, t, J=6.9 Hz), 3.23 (2H, d,J=5.6 Hz), 4.11 (2H, q, J=6.9 Hz), 4.91 (1H, t, J=5.6 Hz), 7.12-7.48(8H, m), 7.60-7.75 (2H, m), 9.63 (1H, s). White crystal.

Compounds were synthesized in accordance with FIG. 2-9. KOK1118 andKOK1141 were synthesized in the same conditions as used in Step 11,KOK1136 and KOK1146 in Step 12, KOK1145 and KOK1148 in Step 6, KOK1149in Step 4, and KOK1154 in Step 5.

KOK1148

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.18 (3H, t, J=7.3 Hz), 1.59 (3H, d,J=7.3 Hz), 3.35-3.52 (1H, m), 4.03-4.20 (2H, m), 4.82 (1H, d, J=5.1 Hz),7.15-7.53 (8H, m), 7.60-7.70 (2H, m), 9.31 (1H, s). Colorless oilysubstance.

KOK1149

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.23 (3H, t, J=7.3 Hz), 1.31 (3H, d,J=7.3 Hz), 3.06-3.20 (1H, m), 4.10-4.24 (2H, m), 4.29 (1H, d, J=7.3 Hz),5.57 (2H, brs), 7.15-7.32 (5H, m). Colorless oily substance.

KOK1154

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 1.20 (3H, d, J=7.3 Hz), 2.94-3.08 (1H,m), 4.12 (1H, d, J=7.6 Hz), 7.12-7.32 (5H, m), 8.51 (2H, brs). Whitecrystal.

Compounds were synthesized in accordance with FIG. 2-10. KOK1188 wassynthesized in the same conditions as used in Step 9, KOK1190 in Step 6,KOK2022 in Step 7, and KOK2036 in Step 5.

KOK1188

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.45 (1H, dd, J=14.5, 7.6 Hz), 3.66 (1H,dd, J=14.5, 7.9 Hz), 3.75 (3H, s), 4.50 (1H, dd, J=7.9, 7.6 Hz),7.50-7.60 (1H, m), 7.65-7.75 (1H, m), 7.75-7.85 (1H, m), 7.98-8:05 (1H,m), 8.05-8.14 (1H, m), 8.80 (1H, d, J=2.3 Hz). Brown oily substance.

KOK1190

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.40 (1H, dd, J=15.2, 6.6 Hz), 3.51 (1H,dd, J=15.2, 4.6 Hz), 3.74 (3H, s), 5.02 (1H, dd, J=6.6, 4.6 Hz),7.33-7.44 (2H, m), 7.44-7.58 (2H, m), 7.60-7.75 (3H, m), 7.75-7.86 (1H,m), 8.06 (1H, d, J=8.6 Hz), 8.26 (1H, s), 8.79 (1H, d, J=2.3 Hz), 9.49(1H, s). White crystal.

KOK2022

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.25 (3H, t, J=7.3 Hz), 3.10-3.29 (2H,m), 4.23 (2H, q, J=7.3 Hz), 4.46 (1H, dd, J=8.2, 5.0 Hz), 5.72 (2H,brs), 7.48-7.57 (1H, m), 7.62-7.72 (1H, m), 7.72-7.82 (1H, m), 8.01 (1H,d, J=2.0 Hz), 8.08 (1H, d, J=8.6 Hz), 8.80 (1H, d, J=2.0 Hz). Lightbrown oily substance.

KOK2036

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 3.06 (1H, dd, J=14.6, 8.4 Hz), 3.19(1H, dd, J=14.6, 4.3 Hz), 4.24 (1H, dd, J=8.4, 4.3 Hz), 7.53-7.63 (1H,m), 7.63-7.75 (1H, m), 7.84-8.02 (2H, m), 8.17 (1H, d, J=2.2 Hz), 8.78(1H, d, J=2.2 Hz). White crystal.

In accordance with FIG. 2-11, KOK2017 was synthesized in the sameconditions as used in Step 6.

KOK2017

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 3.15 (2H, d, J=6.9 Hz), 3.54 (3H, s),3.92-4.06 (1H, m), 5.57-5.67 (1H, m), 7.35-7.60 (6H, m), 7.67-7.93 (6H,m), 10.13 (1H, d, J=5.9 Hz). Light yellow sticky oily substance.

Compounds were synthesized in accordance with FIG. 2-12. KOK2043 wassynthesized in the same conditions as used in Step 9, KOK2044 in Step 3,KOK2087 in Step 4 and KOK2090 in Step 5.

KOK2043

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.19 (1H, dd, J=14.2, 7.1 Hz), 3.42 (1H,dd, J=14.2, 8.2 Hz), 3.73 (3H, s), 4.36 (1H, dd, J=8.2, 7.1 Hz),7.04-7.13 (2H, m), 7.39-7.48 (2H, m). White crystal.

KOK2044

¹H-NMR (CDCl₃, 270 MHz) 5 ppm: 3.21-3.38 (2H, m), 3.74 (3H, s), 4.96(1H, t, J=6.9 Hz), 7.18-7.25 (2H, m), 7.40-7.47 (2H, m), 7.70-7.86 (4H,m). White crystal.

KOK2087

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.86-3.04 (2H, m), 3.75 (3H, s), 4.37(1H, dd, J=8.2, 4.8 Hz), 5.67 (2H, s), 7.04-7.12 (2H, m), 7.37-7.44 (2H,m). White crystal.

KOK2090

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.82 (1H, dd, J=14.3, 8.2 Hz), 2.91(1H, dd, J=14.3, 5.1 Hz), 4.15 (1H, dd, J=8.2, 5.1 Hz), 7.13-7.22 (2H,m), 7.40-7.49 (2H, m), 8.34 (2H, brs). White crystal.

Compounds were synthesized in accordance with FIG. 2-13. KOK2067 wassynthesized in the same conditions as used in Step 3, KOK2110 in Step 4and KOK2111 in Step 5. KOK2066 was synthesized in accordance with Step13 shown below.

Synthesis of KOK2066 (Step 13)

1-Phenylpiperazine (216 mg, 1.34 mmol) and ethyl 2-bromoacrylate (239mg, 1.34 mmol) were dissolved in dichloromethane (5 ml) and stirred atroom temperature 16 hours. The reaction solution was directly purifiedby silica gel column chromatography (hexane:ethyl acetate=3:1) to obtainthe titled compound (colorless oily substance: 145 mg, 32%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.30 (3H, t, J=7.1 Hz), 2.58-2.90 (5H,m), 3.07-3.21 (5H, m), 4.18-4.31 (3H, m), 6.80-6.95 (3H, m), 7.18-7.30(2H, m).

KOK2067

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.30 (3H, t, J=7.1 Hz), 2.64-2.87 (4H,m), 2.95 (1H, dd, J=13.9, 4.1 Hz), 3.03-3.23 (5H, m), 4.16-4.36 (2H, m),5.05 (1H, dd, J=7.6, 4.1 Hz), 6.78-6.92 (3H, m), 7.18-7.29 (2H, m),7.68-7.78 (2H, m), 7.78-7.87 (2H, m). Yellow oily substance.

KOK2110

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 1.30 (3H, t, J=7.1 Hz), 2.54-2.88 (6H,m), 3.18 (4H, t, J=5.0 Hz), 4.12-4.34 (2H, m), 4.42 (1H, dd, J=7.8, 3.1Hz), 5.78 (2H, brs), 6.77-6.96 (3H, m), 7.16-7.31 (2H, m). Whitecrystal.

KOK2111

¹H-NMR (CD₃OH, 270 MHz) δ ppm: 2.98-3.10 (6H, m), 3.22-3.34 (4H, m),4.30 (1H, dd, J=7.8, 4.2 Hz), 6.80-6.91 (1H, m), 6.91-7.02 (2H, m),7.18-7.28 (2H, m). White crystal.

Compounds were synthesized in accordance with FIG. 2-14. KOK2115 wassynthesized in the same conditions as used in Step 9, KOK2116 in Step 3,KOK2117 in Step 4 and KOK2118 in Step 5.

KOK2115

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.35 (3H, s), 3.17 (1H, dd, J=14.0, 7.1Hz), 3.42 (1H, dd, J=14.0, 8.2 Hz), 3.73 (3H, s), 4.36 (1H, dd, J=8.2,7.1 Hz), 6.97 (1H, dd, J=8.2, 2.3 Hz), 7.07 (1H, d, J=2.3 Hz), 7.26 (1H,d, J=8.2 Hz). Brown oily substance.

KOK2116

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.34 (3H, s), 3.20-3.36 (2H, m), 3.74(3H, s), 4.97 (1H, t, J=6.9 Hz), 7.08 (1H, dd, J=8.2, 2.1 Hz), 7.20 (1H,d, J=2.1 Hz), 7.26 (1H, d, J=8.2 Hz), 7.70-7.86 (4H, m). Colorless oilysubstance.

KOK2117

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.34 (3H, s), 2.89 (1H, dd, J=14.3, 8.4Hz), 2.98 (1H, dd, J=14.3, 4.6 Hz), 3.75 (3H, s), 4.37 (1H, dd, J=8.4,4.6 Hz), 5.67 (2H, s), 6.97 (1H, dd, J=8.1, 2.1 Hz), 7.07 (1H, d, J=2.1Hz), 7.25 (1H, d, J=8.1 Hz). White crystal.

KOK2118

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.28 (3H, s), 2.73 (1H, dd, J=14.3, 9.1Hz), 2.94 (1H, dd, J=14.3, 3.6 Hz), 3.98 (1H, dd, J=9.1, 3.6 Hz), 7.07(1H, d, J=8.1, 2.0 Hz), 7.19 (1H, d, J=2.0 Hz), 7.26 (1H, d, J=8.1 Hz).White crystal.

KOK1114 was synthesized in accordance with FIG. 2-1 (Step 14).

KOK1114

KOK1101 (100 mg, 0.307 mmol) was suspended in a 1N aqueous sodiumhydroxide solution (0.6 ml) and stirred at room temperature for 16hours. Insoluble material was filtered off and the filtrate wasconcentrated under reduced pressure, then dried to obtain the titledcompound (white crystal: 115 mg, 100%).

¹H-NMR (D₂O, 270 MHz) δ ppm: 3.04 (2H, d, J=5.6 Hz), 4.48 (1H, t, J=5.6Hz), 7.10-7.50 (10H, m). White crystal.

Compounds were synthesized in accordance with FIG. 2-15. KOK2120 wassynthesized in the same conditions as used in Step 3, KOK2121 in Step 4and KOK2122 in Step 5.

KOK2120

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.38 (3H, s), 3.26 (1H, dd, J=14.5, 7.3Hz), 3.37 (1H, dd, J=14.5, 7.3 Hz), 3.74 (3H, s), 4.93 (1H, t, J=7.3Hz), 7.08-7.23 (3H, m), 7.70-7.86 (4H, m). White crystal.

KOK2121

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.30 (3H, s), 2.82-3.02 (2H, m), 3.74(3H, s), 4.35 (1H, dd, J=8.4, 5.3 Hz), 5.67 (2H, s), 7.03-7.15 (3H, m).Light brown oily substance.

KOK2122

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.26 (3H, s), 2.75-2.94 (2H, m), 4.14(1H, dd, J=8.2, 5.3 Hz), 7.08-7.22 (3H, m). White crystal.

Compounds were synthesized in accordance with FIG. 2-16. KOK2153 wassynthesized in the same conditions as used in Step 3, KOK2154 in Step 4and KOK2155 in Step 5.

KOK2153

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.20-3.38 (2H, m), 3.76 (3H, s), 4.96(1H, t, J=6.4 Hz), 7.21 (1H, dd, J=8.2, 2.1 Hz), 7.39 (1H, d, J=8.2 Hz),7.47 (1H, d, J=2.1 Hz), 7.70-7.88 (4H, m). White crystal.

KOK2154

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.80-3.10 (2H, m), 2.76 (3H, s),4.27-4.45 (1H, m), 5.69 (2H, s), 6.98-7.13 (1H, m), 7.20-7.43 (2H, m).Yellow oily substance.

KOK2155

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.80-3.02 (2H, m), 4.18 (1H, dd, J=8.4,4.6 Hz), 7.23 (1H, dd, J=8.2, 2.0 Hz), 7.50 (1H, d, J=2.0 Hz), 7.53 (1H,d, J=8.2 Hz). White crystal.

Compounds were synthesized in accordance with FIG. 2-17. KOK2157 wassynthesized in the same conditions as used in Step 10, KOK2166 in Step11, KOK2168 in Step 12, KOK2169 in Step 3, KOK2172 in Step 4 and KOK2173in Step 5.

KOK2157

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.62 (1H, d, J=1.8 Hz), 3.84 (3H, s),3.91 (3H, s), 4.23 (1H, d, J=1.8 Hz), 7.08-7.19 (2H, m), 7.27 (1H, dd,J=8.4, 1.8 Hz), 7.66-7.76 (3H, m). White crystal.

KOK2166.

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.75 (1H, brs), 3.02 (1H, dd, J=14.7, 4.5Hz), 3.18 (1H, dd, J=14.7, 4.5 Hz), 3.69 (3H, s), 3.83 (3H, s),4.40-4.49 (1H, m), 7.00-7.10 (2H, m), 7.23 (1H, dd, J=8.4, 1.8 Hz), 7.52(1H, s), 7.60 (2H, d, J=8.4 Hz). White crystal.

KOK2168

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.35 (1H, dd, J=14.0, 6.9 Hz), 3.58 (1H,dd, J=14.0, 8.6 Hz), 3.69 (3H, s), 3.89 (3H, s), 4.48 (1H, dd, J=8.6,6.9 Hz), 7.07-7.16 (2H, m), 7.27 (1H, dd, J=8.4, 1.7 Hz), 7.58 (1H, s),7.67 (2H, d, J=7.9 Hz). Light yellow oily substance.

KOK2169

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.38-3.55 (2H, m), 3.70 (3H, s), 3.86(3H, s), 5.08 (1H, t, J=6.9 Hz), 7.04-7.13 (2H, m), 7.40 (1H, dd, J=8.4,1.7 Hz), 7.61-7.79 (7H, m). White crystal.

KOK2172

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.02-3.21 (2H, m), 3.73 (3H, s), 3.90(3H, s), 4.48 (1H, dd, J=8.4, 5.0 Hz), 5.67 (2H, s), 7.07-7.15 (2H, m),7.31 (1H, dd, J=8.4, 1.7 Hz), 7.58 (1H, s), 7.67 (2H, d, J=8.4 Hz).White crystal.

KOK2173

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.96 (1H, dd, J=14.2, 8.4 Hz), 3.07(1H, dd, J=14.2, 4.8 Hz), 3.85 (3H, s), 4.25 (1H, dd, J=8.4, 4.8 Hz),7.12 (1H, dd, J=8.9, 2.6 Hz), 7.27 (1H, d, J=2.5 Hz), 7.35 (1H, dd,J=8.6, 1.4 Hz), 7.64 (1H, s), 7.67-7.78 (2H, m). White crystal.

Compounds were synthesized in accordance with FIG. 2-18.

Synthesis of KOK3045 (Step 15)

Methyl 3-(4-bromophenyl)-2-hydroxy propionate (360 mg, 1.389 mmol),p-chlorophenylboronic acid (326 mg, 2.084 mmol),[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II),dichloromethane adduct (57 mg, 0.07 mmol), potassium carbonate (288 mg,2.084 mmol) and dioxane (5 ml) were stirred under a nitrogen atmosphereat 90° C. for 3 hours. The reaction solution was concentrated underreduced pressure and directly purified by silica gel chromatography(hexane:ethyl acetate=4:1) to obtain the titled compound (white crystal:284 mg, 70%).

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.75 (1H, d, J=6.1 Hz), 3.00 (1H, dd,J=14.0, 6.9 Hz), 3.18 (1H, dd, J=14.0, 4.3 Hz), 3.80 (3H, s), 4.44-4.53(1H, m), 7.25-7.32 (2H, m), 7.35-7.42 (2H, m), 7.45-7.52 (4H, m). Whitecrystal.

KOK3049 was synthesized in the same conditions as used in Step 12,KOK3050 in Step 3, KOK3052 in Step 4 and KOK3053 in Step 5.

KOK3049

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.28 (1H, dd, J=14.0, 7.1 Hz), 3.51 (1H,dd, J=14.0, 8.2 Hz), 3.75 (3H, s), 4.43 (1H, dd, J=8.2, 7.1 Hz),7.20-7.56 (8H, m). Colorless oily substance.

KOK3050

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.30-3.47 (2H, m), 3.75 (3H, s), 5.05(1H, t, J=6.9 Hz), 7.34-7.44 (4H, m), 7.44-7.53 (4H, m), 7.70-7.86 (4H,m). White solid substance.

KOK3052

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 2.95-3.13 (2H, m), 3.77 (3H, s), 4.45(1H, dd, J=8.4, 4.8 Hz), 5.69 (2H, s), 7.25-7.32 (2H, m), 7.35-7.42 (2H,m), 7.44-7.53 (4H, m). White crystal.

KOK3053

¹H-NMR (DMSO-d₆, 270 MHz) δ ppm: 2.81-3.03 (2H, m), 4.22 (1H, dd, J=8.2,5.0 Hz), 7.28-7.36 (2H, m), 7.45-7.53 (2H, m), 7.53-7.62 (2H, m),7.62-7.72 (2H, m). White crystal.

KOK2165 was synthesized in accordance with FIG. 2-19. KOK2165 wassynthesized in the same conditions as used in Step 6.

¹H-NMR (CDCl₃, 270 MHz) δ ppm: 3.05-3.25 (2H, m), 3.63 (3H, s), 4.89(1H, t, J=6.1 Hz), 7.19 (4H, s), 7.27-7.38 (2H, m), 7.38-7.50 (1H, m),7.63-7.75 (2H, m), 10.07 (1H, s). Brown oily substance.

2. Use Examples (1) Quantification of Endogenous IAA Amount Arabidopsis

Arabidopsis (col-0) was cultured in a plate horizontally set and using ½MS medium containing 1.0% sucrose and 0.8% agar under continuous whitelight at 22° C. for 6 days, and thereafter subjected to liquid shakingculture in ½ MS medium containing 1.0% sucrose under continuous whitelight at 22° C. for 24 hours. Subsequently, the compound of the presentinvention (30 μM) was added to the medium and subjected to liquidshaking culture under continuous white light at 22° C. for 3 hours toquantify IAA endogenous amount. The IAA endogenous amount was measuredby use of LC-MS/MS in accordance with the method of Soeno et al. (PlantCell Physiology 51: 524-536 (2010)). The results are shown in FIG. 3.

(2-1) Growth Test Arabidopsis

Arabidopsis was cultured in a plate vertically set and using ½ MS mediumcontaining 1.5% sucrose, 0.8% agar and the compound of the presentinvention (30 μM) under continuous white light at 22° C. for 8 days.Morphology of arabidopsis was observed to evaluate the effect of thecompound of the present invention.

The results are shown in Table 1. Morphologies of arabidopsis whosegrowth was inhibited compared to DMSO control plant are shown in FIG. 4.

TABLE 1 Inhibitor Growth inhibitory effect L-AOPP KOK 1101 ◯ KOK 1108 ◯KOK 1114 KOK 1145 KOK 1148 KOK 1149 KOK 1154 KOK 1157 ◯ KOK 1160 ◯ KOK1161 ◯ KOK 1162 ◯ KOK 1165 ◯ KOK 1166 ◯ KOK 1167 ◯ KOK 1168 ◯ KOK 1169 ◯KOK 1172 ◯ KOK 1174 ◯ KOK 1175 ◯ KOK 1176 ◯ KOK 1178 ◯ KOK 1179 ◯ KOK1180 KOK 1183 ◯ KOK 1185 ◯ KOK 1186 ◯ KOK 1187 ◯ KOK 1190 KOK 1194 ◯ KOK1198 ◯ KOK 2011 ◯ KOK 2015 ◯ KOK 2016 ◯ KOK 2017 ◯ KOK 2021 ◯ KOK 2022KOK 2026 ◯ KOK 2027 ◯ KOK 2029 ◯ KOK 2030 ◯ KOK 2031 ◯ KOK 2036 KOK 2044◯ KOK 2067 KOK 2087 KOK 2090 KOK 2110 KOK 2111 KOK 2116 ◯ KOK 2117 KOK2118 KOK 2120 ◯ KOK 2121 KOK 2122 ◯ KOK 2153 ◯ KOK 2154 ◯ KOK 2155 ◯ KOK2165 ◯ KOK 2169 ◯ KOK 2172 ◯ KOK 2173 KOK 3050 KOK 3052 ◯ KOK 3053 ◯ ◯:Growth inhibition was observed compared to DMSO control plant

(2-2) Growth Test Arabidopsis

Arabidopsis was cultured in a plate vertically set and using ½ MS mediumcontaining 1.5% sucrose, 0.8% agar and the compound of the presentinvention (100 μM) under continuous white light at 22° C. for 8 days.Morphology of arabidopsis was observed to evaluate the effect of thecompound of the present invention.

Compounds in the presence of which arabidopsis rarely grew are shown inTable 2.

TABLE 2 KOK 1157 KOK 1162 KOK 1174 KOK 1178 KOK 1183 KOK 1185 KOK 1186KOK 1194 KOK 1198 KOK 2011 KOK 2017 KOK 2044 KOK 2165 KOK 2172

(3) Growth Recovery Test Arabidopsis

Arabidopsis was cultured in a plate vertically set and using ½ MS mediumcontaining 1.5% sucrose, 0.8% agar (0.6% Gelrite in the case ofKOK1169), the compound of the present invention and IAA under continuouswhite light at 22° C. for 8 days. Morphology of arabidopsis was observedto evaluate the recovery of the plant growth suppressed by the compoundof the present invention.

In the test, KOK1101 (30 μM), KOK1160 (30 μM), KOK1165 (30 μM), andKOK1169 (100 μM) were studied. The morphologies of arabidopsis culturedare shown in FIG. 5.

In the case of growth inhibition by KOK1101 (30 μM), main rootelongation was recovered by simultaneous application with IAA (10 nM)and growth of an aerial part was recovered by simultaneous applicationwith IAA (100 nM).

In the case of growth inhibition by KOK1160 (30 μM), growth of an aerialpart and main root elongation were recovered by simultaneous applicationwith IAA (10 nM).

In the case of growth inhibition by KOK1165 (30 μM), growth of an aerialpart and main root elongation were recovered by simultaneous applicationwith IAA (10 nM)

In the case of growth inhibition by KOK1169 (100 μM), growth of anaerial part and main root elongation were recovered by simultaneousapplication with IAA (10 nM).

(4) Growth Test Tobacco

Tobacco was cultured in a plate vertically set and using ½ MS mediumcontaining 1.5% sucrose and 0.8% agar under continuous white light at25° C. for 7 days. Thereafter, tobacco was transferred to a platevertically set and using ½ MS medium containing 1.5% sucrose, 0.8% agarand the compound of the present invention (100 μM) and cultured undercontinuous white light at 25° C. for 7 days. Morphology of tobacco wasobserved to evaluate plant growth inhibitory effect of the compound ofthe present invention.

The results are shown in Table 3. Morphologies of tobacco whose growthis inhibited compared to DMSO control plant are shown in FIG. 6 (in FIG.6, “preculture” shows seedling right before transplant).

TABLE 3 Inhibitor Growth inhibitory effect Note L-AOPP X KOK 1101 ◯ KOK1108 ◯ KOK 1145 X KOK 1157 ◯ KOK 1160 ◯ KOK 1165 ◯ KOK 1167 ◯Auxin-excess like morphology KOK 1168 ◯ KOK 1169 X KOK 1174 ◯ KOK 1176 XKOK 1178 ◯ KOK 1180 X KOK 1183 ◯ KOK 1185 ◯ KOK 1187 ◯ Auxin-excess likemorphology KOK 1190 ◯ KOK 2011 ◯ KOK 2029 X KOK 2031 ◯ ◯: Growthinhibition was observed compared to DMSO control plant

(5) Growth Test Lettuce

Lettuce was cultured in a plate vertically set and using ½ MS mediumcontaining 1.5% sucrose, 0.8% agar and KOK1101 (30 μM) under continuouswhite light at 25° C. for 6 days. Morphology of lettuce was observed toevaluate plant growth inhibitory effect of the compound of the presentinvention.

Morphologies of lettuce cultured by use of KOK1101 are shown in FIG. 7.Apparent growth inhibition was observed in the aerial part, whereas, inan underground part, promotion of main root elongation and inhibition ofroot hair formation were observed.

(6) Protein Activity Inhibitory Test

The inhibitory activities of the compound of the present inventionagainst an IAA biosynthesis enzyme, tryptophan aminotransferase (TAA1),and phenylalanineammonia-lyase (PAL) of arabidopsis were evaluated.

(i) TAA1 Inhibitory Test

The test was carried out in accordance with a method described in Cell(2008); 133: pp. 164-176. Specifically, borate buffer (pH 8.5) of afinal concentration of 0.5 M, L-Trp (0.3 mM), sodium pyruvate (1 mM),PLP (10 μM), TAA1 (1 μg) and the compound of the present invention (1μM) were reacted at 35° C. for 30 minutes. Thereafter, 6N HCl (20 μL)was added to terminate the reaction, A330 was measured.

Blank=(−) TAA1 (0.5M Borate buffer (pH 8.5) was used as blank inspectrophotometry).

The results are shown in FIG. 8. In the test (in vitro), it was observedthat a compound having a free carboxylic acid and a free amine as thecarboxyl group and the amino group, respectively, tends to stronglyinhibit TAA1. It is presumed that, even a compound having a protectedcarboxyl group and a protected amino group may inhibit TAA 1 due toremoving the protecting groups in the plant body.

(ii) AtPAL2 Inhibitory Test

The test was carried out in accordance with a method described inPhytochem. (2004); 65: pp. 1557-1564, and J. Plant Physiol. (2008); 165:pp. 1491-1499. Specifically, borate buffer (pH 8.5) of a finalconcentration of 0.1 M, L-Phe (0.06 mM (or 60 μM)), PAL2 (0.5 μg) andthe compound of the present invention (15 nM, volume: 500 μL (1% DMSO))were reacted at 35° C. for 15 minutes. Thereafter, 1N HCl (20 μL) wasadded to terminate the reaction, A290 was measurement.

Blank=0.1M Borate buffer (pH 8.5) (no change in value at (+) thecompound (−) PAL2. No change in value at (+) heat inactivated enzyme).

The results are shown in FIG. 9. In the case where the phenyl group ofL-AOPP has a large substituent or is modified to a larger ring, it wasobserved that PAL2 inhibitory activity tends to be low.

(7) Growth Test Rice

Rice (Nipponbare) at the 6th day after transferred to a KOK1168 (50μM)-containing medium is shown in FIG. 10 (right figure) (left figureshows DMSO control plant). Growth of seedling treated by KOK1168 wasremarkably inhibited.

(8) Growth Test Tomato

Tomato (Momotaro) at the 6th day after transferred to a plate containingKOK1168 (100 μM) is shown in FIG. 11 (right figure) (left figure showsDMSO control plant). Growth of seedling treated by KOK1168 wasremarkably inhibited.

(9) Growth Test Physcomitrella patens Subsp. Patens

Physcomitrella patens subsp. patens at the 7th day after transferred toa plate containing KOK1168 (100 μM) is shown in FIG. 12 (right figure)(left figure shows DMSO control plant). Growth of protonemata wasremarkably inhibited and differentiation into forage was also inhibitedby the treatment with KOK1168.

INDUSTRIAL APPLICABILITY

According to the present invention, an auxin biosynthesis inhibitorsuperior to L-AOPP can be provided.

All publications, patents and patent applications cited in thespecification are incorporated herein in their entirety.

The invention claimed is:
 1. A compound represented by general formula(I):

wherein R¹ is chlorophenyl, bromophenyl, biphenyl, phenoxyphenyl,4-chloro-3-methylphenyl, 4-chloro-2-methylphenyl, dichlorophenyl,6-methoxy-2-naphthyl, naphthyl or quinolinyl; R² is a C₁₋₆ alkyl group;R³ and R⁴ are each hydrogen, or R³ is hydrogen and R⁴ is acetyl orbenzoyl, or R³ and R⁴ together form propan-2-ylidene or R³ and R⁴,together with a nitrogen atom to which R³ and R⁴ are bound, formphthalimide or succinimide; R⁵ is hydrogen; and X is O, or a salt orsolvate thereof.
 2. The compound according to claim 1, wherein R¹ is2-naphthyl, R² is methyl, R³ and R⁴ are each hydrogen or R³ and R⁴,together with a nitrogen atom to which R³ and R⁴ are bound, formphthalimide, R⁵ is hydrogen, and X is O.
 3. A method for inhibitingbiosynthesis of auxin in a plant, comprising applying the compoundaccording to claim 1 to the plant.
 4. A method for inhibiting tryptophanaminotransferase in a plant, comprising applying the compound accordingto claim 1 to the plant.
 5. A method for inhibiting tryptophanaminotransferase, comprising bringing the compound according to claim 1into contact with the tryptophan aminotransferase in vitro.
 6. A methodfor regulating growth of a plant, comprising applying the compoundaccording to claim 1 to the plant.
 7. A method for weeding a plant,comprising applying the compound according to claim 1 to the plant.